Differential modulation of response properties of vestibular afferents by cholinergic and GABAergic efferents.

胆碱能和 GABA 能传出神经对前庭传入神经反应特性的差异调节。

• 批准号: 9185967
• 负责人: Soroush Sadeghi Ghandehari
• 金额: $ 15.95万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-01 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9185967
• 关键词: Address; Affect; Agonist; Animals; Area; Bilateral; Brain; Brain Stem; Cholinergic Antagonists; Cholinergic Fibers; Code; Complement; Data; Detection; Drug usage; Efferent Pathways; Electrophysiology (science); Epithelium; Feedback; Fiber; Financial compensation; Frequencies; Functional disorder; Future; G-substrate; GTP-Binding Protein alpha Subunits, Gs; Ganglia; Goals; Head Movements; Immunohistochemistry; In Vitro; Intraperitoneal Injections; Label; Light; Mammals; Measures; Mediating; Membrane; Motion Sickness; Movement; Mus; Muscarinic Acetylcholine Receptor; Muscarinic Antagonists; Nerve; Neurons; Pathologic; Pathway interactions; Patients; Pattern; Peripheral; Pharmaceutical Preparations; Pharmacology; Phase; Play; Potassium; Potassium Channel; Property; Rattus; Rest; Rhodopsin; Role; Rotation; Seizures; Sensory; Side; Signal Transduction; Stimulus; Synapses; System; Testing; Therapeutic; Type II Hair Cell; Vestibular Hair Cells; Vestibular Nerve; Vestibular ganglion; afferent nerve; base; behavior measurement; cholinergic; experimental study; extracellular; genetic approach; improved; in vivo; knockout animal; nerve supply; optogenetics; patch clamp; public health relevance; receptor; response; sensory system; vestibular pathway; voltage; wortmannin

 DESCRIPTION (provided by applicant): Vestibular receptors encode information about head movements and send these signals through the vestibular nerve to the brain stem. In turn, receptors and afferents receive bilateral inputs from efferent fibers that originate in the brain stem. To date, the function of the efferent pathway has remained elusive. It has been suggested that efferents might provide information regarding imbalance in the activity on the two sides and play a role in vestibular compensation. In particular, efferents mainly affect activity of afferent with calyx terminals, which completely cover the basolateral walls of vestibular hair cells and provide a unique form of synapse present only in the vestibular periphery. Furthermore, there are two main types of efferent fibers, cholinergic and GABAergic. However, almost nothing is known regarding the innervation patterns, synaptic properties, receptor types, and differential effects of the two efferent pathways on vestibular afferent sensory coding. The goal of the present proposal is to investigate changes in afferent response properties mediated by efferent inputs from these two pathways and the underlying cellular mechanisms. The hypothesis, supported by preliminary results, is that efferent inputs change the firing properties and response patterns of afferents from phasic to tonic. The effect of muscarinic acetylcholine receptors (mAChR) on calyx membrane properties will be studied at the cellular level in vitro. Preliminary data suggest that activation of mAChRs results in a shift to tonic afferent responses mediated by changes in potassium channel activities present in calyces. The effect of GABAergic efferent inputs on membrane properties of calyx terminals will also be investigated in vitro. Preliminary results suggest that ~50% of calyces do not receive cholinergic efferents and might receive GABAergic inputs. Finally, the effect of the two efferent pathways will be studied on firing properties of afferent fibers in response to rotational movements in live animals (in vivo). Results of the experiments in this proposal can provide a leap in our understanding of feedback modulation of sensory coding in this example sensory system. This will be the basis for future studies in alert behaving animals in order to correlate neuronal and behavioral measures as well as studying the possible role of efferent inputs in vestibular compensation.

 描述（由申请人提供）：前庭感受器编码有关头部运动的信息，并通过前庭神经将这些信号发送到脑干。反过来，受体和传入神经接受来自脑干传出纤维的双侧输入。迄今为止，传出通路的功能仍然难以捉摸。有人认为，传出神经可能提供有关活动不平衡的信息，并在前庭补偿中发挥作用。特别地，传出神经主要影响具有花萼终末的传入神经的活动，花萼终末完全覆盖前庭毛细胞的基底外侧壁，并且提供仅存在于前庭外周中的独特形式的突触。此外，有两种主要类型的传出纤维，胆碱能和GABA能。然而，几乎没有什么是已知的神经支配模式，突触特性，受体类型，和前庭传入感觉编码的两个传出通路的差异影响。本研究的目的是探讨这两条通路的传出输入介导的传入反应特性的变化及其细胞机制。初步结果支持的假设是，传出输入改变了传入的放电特性和反应模式，从相位到紧张。毒蕈碱型乙酰胆碱受体（mAChR）对萼膜特性的影响将在体外细胞水平上进行研究。初步数据表明，激活mAChRs的结果在转变为紧张性传入反应介导的钾通道活动的变化存在于肾盏。GABA能传出输入对萼终末膜特性的影响也将在体外研究。初步结果表明，约50%的肾盏不接受胆碱能传出，可能接受GABA能输入。最后，我们将在活体动物上研究这两条传出通路对传入纤维响应旋转运动的放电特性的影响 (in体内）。在这个建议的实验结果可以提供一个飞跃，在我们的理解反馈调制的感觉编码在这个例子的感觉系统。这将是未来研究的基础，在警觉行为的动物，以相关的神经元和行为的措施，以及研究可能的作用，传出输入前庭补偿。